Monocyte chemoattractant protein 1 as a potential biomarker for immune checkpoint inhibitor-associated neurotoxicity.
biomarker
immune-related adverse events
immunotherapy
neurotoxicity
serum neurofilament light chains
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
revised:
25
01
2023
received:
29
11
2022
accepted:
02
02
2023
medline:
10
5
2023
pubmed:
17
2
2023
entrez:
16
2
2023
Statut:
ppublish
Résumé
Oncological patients can benefit substantially from treatment with immune checkpoint inhibitors (ICI). However, there is a growing awareness of immune-related adverse events (irAE). Especially ICI-mediated neurological adverse events (nAE(+)), are tough to diagnose and biomarkers to identify patients at risk are missing. A prospective register with prespecified examinations was established for ICI treated patients in December 2019. At the time of data cut-off, 110 patients were enrolled and completed the clinical protocol. Herein, cytokines and serum neurofilament light chain (sNFL) from 21 patients were analyzed. nAE of any grade were observed in 31% of the patients (n = 34/110). In nAE(+) patients a significant increase in sNFL concentrations over time was observed. Patients with higher-grade nAE had significantly elevated serum-concentrations of monocyte chemoattractant protein 1 (MCP-1) and brain-derived neurotrophic factor (BDNF) at baseline compared to individuals without any nAE (p < 0.01 and p < 0.05). Here, we identified nAE to occur more frequently than previously reported. Increase of sNFL during nAE confirms the clinical diagnosis of neurotoxicity and might be a suitable marker for neuronal damage associated with ICI therapy. Furthermore, MCP-1 and BDNF are potentially the first clinical-class nAE predictors for patients under ICI therapy.
Sections du résumé
BACKGROUND
Oncological patients can benefit substantially from treatment with immune checkpoint inhibitors (ICI). However, there is a growing awareness of immune-related adverse events (irAE). Especially ICI-mediated neurological adverse events (nAE(+)), are tough to diagnose and biomarkers to identify patients at risk are missing.
METHODS
A prospective register with prespecified examinations was established for ICI treated patients in December 2019. At the time of data cut-off, 110 patients were enrolled and completed the clinical protocol. Herein, cytokines and serum neurofilament light chain (sNFL) from 21 patients were analyzed.
RESULTS
nAE of any grade were observed in 31% of the patients (n = 34/110). In nAE(+) patients a significant increase in sNFL concentrations over time was observed. Patients with higher-grade nAE had significantly elevated serum-concentrations of monocyte chemoattractant protein 1 (MCP-1) and brain-derived neurotrophic factor (BDNF) at baseline compared to individuals without any nAE (p < 0.01 and p < 0.05).
CONCLUSION
Here, we identified nAE to occur more frequently than previously reported. Increase of sNFL during nAE confirms the clinical diagnosis of neurotoxicity and might be a suitable marker for neuronal damage associated with ICI therapy. Furthermore, MCP-1 and BDNF are potentially the first clinical-class nAE predictors for patients under ICI therapy.
Identifiants
pubmed: 36794673
doi: 10.1002/cam4.5695
pmc: PMC10166892
doi:
Substances chimiques
Immune Checkpoint Inhibitors
0
Brain-Derived Neurotrophic Factor
0
Chemokine CCL2
0
Biomarkers
0
Cytokines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
9373-9383Informations de copyright
© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Références
Int J Mol Sci. 2020 Oct 21;21(20):
pubmed: 33096634
N Engl J Med. 2015 Nov 5;373(19):1803-13
pubmed: 26406148
J Immunother Cancer. 2019 May 22;7(1):134
pubmed: 31118078
Cancer Immunol Immunother. 2022 Apr;71(4):769-775
pubmed: 34515815
Lung Cancer. 2018 Jun;120:98-107
pubmed: 29748024
Clin Cancer Res. 2015 Oct 1;21(19):4286-93
pubmed: 25977344
J Clin Immunol. 2003 Jul;23(4):259-67
pubmed: 12959218
Neurol Neuroimmunol Neuroinflamm. 2019 Aug 7;6(6):
pubmed: 31454760
N Engl J Med. 2018 Jan 11;378(2):158-168
pubmed: 29320654
Br J Cancer. 2019 Jan;120(1):63-68
pubmed: 30377338
J Immunother. 2015 Jan;38(1):37-9
pubmed: 25415286
Front Neurol. 2015 May 26;6:110
pubmed: 26074866
Mol Neurobiol. 2019 May;56(5):3295-3312
pubmed: 30117106
Curr Opin Neurol. 2019 Jun;32(3):500-510
pubmed: 30893101
N Engl J Med. 2016 Nov 10;375(19):1856-1867
pubmed: 27718784
Cancer Med. 2023 Apr;12(8):9373-9383
pubmed: 36794673
J Neuroimmunol. 2002 May;126(1-2):205-12
pubmed: 12020972
Eur J Cancer. 2017 Mar;73:1-8
pubmed: 28064139
Int Immunopharmacol. 2021 Dec;101(Pt B):107598
pubmed: 34233864
Sci Rep. 2019 Oct 1;9(1):14039
pubmed: 31575933
Ann Rheum Dis. 2018 Mar;77(3):393-398
pubmed: 29146737
Brain Pathol. 2009 Jul;19(3):392-8
pubmed: 18637012
Oncotarget. 2016 May 10;7(19):28697-710
pubmed: 26885690
Oncologist. 2017 Jun;22(6):709-718
pubmed: 28495807
N Engl J Med. 2015 Jan 22;372(4):320-30
pubmed: 25399552
N Engl J Med. 2016 Nov 10;375(19):1823-1833
pubmed: 27718847
Lung Cancer. 2019 Jun;132:107-113
pubmed: 31097082
Mol Psychiatry. 2011 Nov;16(11):1088-95
pubmed: 20856249
Ann Neurol. 2020 May;87(5):659-669
pubmed: 32086972
BioDrugs. 2016 Dec;30(6):571-584
pubmed: 27848165
Neurology. 2017 Nov 28;89(22):2230-2237
pubmed: 29079686
Circulation. 2019 Jan 8;139(2):256-268
pubmed: 30586705
Expert Opin Ther Targets. 2003 Feb;7(1):35-48
pubmed: 12556201
Cancer Immunol Immunother. 2020 Sep;69(9):1813-1822
pubmed: 32350592
Clin Exp Dermatol. 2019 Aug;44(6):643-646
pubmed: 30618056
Clin Cancer Res. 2012 Dec 15;18(24):6580-7
pubmed: 23087408
Biomedicines. 2020 Aug 28;8(9):
pubmed: 32872144
Onco Targets Ther. 2018 Feb 23;11:955-965
pubmed: 29503570
J Clin Invest. 2015 Sep;125(9):3335-7
pubmed: 26325031
Curr Alzheimer Res. 2019;16(4):344-352
pubmed: 30961497
Ann Neurol. 2017 Jun;81(6):857-870
pubmed: 28512753
N Engl J Med. 2017 Jun 8;376(23):2304
pubmed: 28591526
Rev Med Interne. 2016 Oct;37(10):694-700
pubmed: 27370898
Oncologist. 2019 Apr;24(4):435-443
pubmed: 30482825